Relationship of Asymmetric Dimethylarginine With Penile Doppler Ultrasound Parameters in Men with Vasculogenic Erectile Dysfunction

Abstract

BackgroundAsymmetric dimethylarginine (ADMA), a selective endogenous nitric oxide synthase inhibitor, is elevated in many conditions associated with erectile dysfunction (ED), such as hypertension, diabetes, hyperlipidemia, and renal failure; it is also increased in men with coronary artery disease and ED. The dynamic penile colour Doppler ultrasound is considered the gold standard for the evaluation of penile vascular damage. ObjectiveWe investigated whether the extent of ultrasonographically documented penile vascular disease is associated with higher ADMA levels. Design, setting, and participantsOne hundred four consecutive ED patients (mean age: 56±9 yr) without manifest cardiovascular/atherosclerotic disease and 31 subjects with normal erectile function matched for age and traditional risk factors were studied. MeasurementsWe evaluated penile dynamic colour Doppler parameters of arterial insufficiency (peak systolic velocity) and veno-occlusive dysfunction (end diastolic velocity) and measured systemic inflammatory markers/mediators. Results and limitationsCompared to men without ED, ED patients had significantly higher ADMA levels (p<0.001). ADMA was significantly increased in patients with severe arterial insufficiency (PSV<25cm/s) compared to subjects with borderline insufficiency and men with normal penile arterial function (p<0.001, by analysis of variance). Multivariable analysis adjusting for age, mean pressure, other risk factors, high-sensitivity C-reactive protein, testosterone, and treatment showed independent inverse association between ADMA level and peak systolic velocity (p<0.01). The combination of higher ADMA level with arterial insufficiency showed greater impact on 10-yr risk of a cardiovascular event compared to either parameter alone. ConclusionsADMA level is independently associated with ultrasonographically documented poor penile arterial inflow. This finding underlines the important role of ADMA as a marker of penile arterial damage and implies a contribution of this compound to the pathophysiology of generalised vascular disease associated with ED.